Figure 4
Overexpression of UCHL1 decreases plaque formation and improves learning and memory deficits.
(A) Viruses were bilaterally injected into the hippocampal region of APP23/PS45 mice at the age of seven weeks old. The mice were then sacrificed at 17 weeks old. Neuritic plaques were detected by 4G8 antibody. The arrows indicate plaques in AAV1-GFP control virus (Aa) or AAV1-UCHL1-GFP injection (Ab). The plaques were confirmed by thioflavin-S staining (Ac and d). (B) Quantification of neuritic plaques in (A, a-b) by Image J (NIH). The value represents mean ± SEM. n = 8 for each group. **p < 0.01 by Student's t-test. (C) Detection of neuritic plaques in the cortical region in AAV1-UCHL1-GFP -injected mice (Cb) and controls (Ca). The plaques were confirmed by thioflavin-S staining (Cc and d). Bar: 500 μm. (D) Quantification of neuritic plaques in (C, a-b). n = 8 for each group. **p < 0.01 by Student's t-test. (E) Neuritic plaques in six-month-old APP23 and APP23/gad mice were examined by thioflavin-S staining. (F) Quantification of (E). n = 8 for each group. *p < 0.05 by Student's t-test. (G-J) Eight weeks after AAV1-UCHL1-GFP or AAV1-GFP injection, APP23/PS45 mice were subjected to Morris water maze test at the age of 15 weeks old. n = 16 for AAV1-GFP group, n = 13 for AAV1-UCHL1-GFP group. On the first day of visible platform test, AAV-UCHL1-GFP-injected mice displayed similar escape latency (G) and swimming speed (H) as control mice. p>0.05 by Student's t-test. (I) During hidden platform test, AAV1-UCHL1-GFP mice exhibited shorter escape latency. *p<0.05 by two-way ANOVA group comparison. (J) On day 6 of the probe trial, AAV1-UCHL1-GFP-injected mice spent more time in the target quadrant than controls. *p<0.05 by Student's t-test. The values are expressed as mean ± SEM. (K-N) Six-month-old APP23 or APP23/gad mice were subjected to Morris water maze test. n = 12 for APP23 group, n = 11 for APP23/gad group. (K) Escape latency and (L) swimming speed. P>0.05 by Student's t-test. (M) Hidden platform tests. *p<0.05 by two-way ANOVA post-hoc Bonferroni test. (N) The probe trial on day 6. *p<0.05 by Student's t-test.
